11-66526181-TG-CA

Variant names:

• chr11-66526181-TG-CA
• NM_024649.5:c.1169_1170delTGinsCA
• BBS1 p.Met390Thr

GermlineCancer (beta)

Variant summary

Our verdict is Likely pathogenic.

+6 Likely Pathogenic

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 6 classification points (ACMG Germline Pathogenicity v2019). PM1PM2PM5

The NM_024649.5(BBS1):c.1169_1170delTGinsCA (p.Met390Thr) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. A different missense at the same amino acid position has been reported as Pathogenic/Likely Pathogenic in ClinVar: p.M390R: Pathogenic/Likely_pathogenic (ClinVar VariationId 12143, 2 stars) Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.M390V: Uncertain_significance (ClinVar VariationId 1979201, 1 star)

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS1 NM_024649.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 0 publications found

Genes affected

BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

BBS1 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women's Health, PanelApp Australia, Natera, Ambry Genetics, Genomics England PanelApp, G2P
• BBS1-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000256349 (HGNC:):

ZDHHC24 (HGNC:27387): (zDHHC palmitoyltransferase 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in protein targeting to membrane. Predicted to be located in membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_pathogenic. The variant received 6 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM1Mutational hot spot or critical domain		Missense neighbourhood hotspot (≥2 P/LP within ±8 AA, OR ≥ 5 vs. background) — PM1; In-domain: 0 pathogenic, 0 benign rare missense variants.; ±8 AA neighbourhood: 2 pathogenic, 0 benign (OR vs. background: 25.0).
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (base 0.001, raised to 0.00268 by highest known P/LP ClinVar AF 0.00268) — PM2 moderate.
	PM5Novel missense at known pathogenic residue		Different pathogenic missense at same AA residue in ClinVar (PM5); ClinVar contains a germline Pathogenic/Likely Pathogenic entry at the same amino acid position with a different amino acid change: p.M390R: Pathogenic/Likely_pathogenic (ClinVar VariationId 12143, 2 stars); Other variants at the same amino acid residue (not pathogenic): p.M390V: Uncertain_significance (ClinVar VariationId 1979201, 1 star)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_024649.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BBS1 NM_024649.5	MANE Select	c.1169_1170delTGinsCA p.Met390Thr	missense	N/A	Prot: NP_078925.3
	ZDHHC24 NM_001348571.2		c.*21+754_*21+755delCAinsTG	intron	Intron 4 of 4	Prot: NP_001335500.1 UniProt:

BBS1 NM_024649.5

MANE Select

HGVSc / HGVSpc.1169_1170delTGinsCAp.Met390Thr

Exon rankN/A

missense

Prot: NP_078925.3

ZDHHC24 NM_001348571.2

HGVSc / HGVSpc.*21+754_*21+755delCAinsTG

Exon rankIntron 4 of 4

intron

Prot: NP_001335500.1UniProt: E9PLR9

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BBS1 ENST00000318312.12	TSL:1MANE Select	c.1169_1170delTGinsCA p.Met390Thr	missense	N/A	Prot: ENSP00000317469.7 UniProt:
	ENSG00000256349 ENST00000419755.3	TSL:2	c.1280_1281delTGinsCA p.Met427Thr	missense	N/A	Prot: ENSP00000398526.3 UniProt:
	BBS1 ENST00000393994.4	TSL:1	c.782_783delTGinsCA p.Met261Thr	missense	N/A	Prot: ENSP00000377563.2 UniProt:

BBS1 ENST00000318312.12

TSL:1MANE Select

HGVSc / HGVSpc.1169_1170delTGinsCAp.Met390Thr

Exon rankN/A

missense

Prot: ENSP00000317469.7UniProt: Q8NFJ9-1

ENSG00000256349 ENST00000419755.3

TSL:2

HGVSc / HGVSpc.1280_1281delTGinsCAp.Met427Thr

Exon rankN/A

missense

Prot: ENSP00000398526.3UniProt: Q8NFJ9-2

BBS1 ENST00000393994.4

TSL:1

HGVSc / HGVSpc.782_783delTGinsCAp.Met261Thr

Exon rankN/A

missense

Prot: ENSP00000377563.2UniProt: Q8NFJ9-3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	5.0

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr11-66293652;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar