X-106821006-C-T

Variant names:

• chrX-106821006-C-T
• rs369240583
• NM_017752.3:c.360+11C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017752.3(TBC1D8B):​c.360+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,034,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 52 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.00017 (0 hom. 51 hem.)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

TBC1D8B (HGNC:24715): (TBC1 domain family member 8B) This gene encodes a protein with a TBC (Tre-2/Bub2/CDC16) domain. Some mammalian proteins with this domain have been shown to function as Rab-GAPs by binding to specific Rab proteins and affecting their GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-106821006-C-T is Benign according to our data. Variant chrX-106821006-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1991736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00017 (157/923505) while in subpopulation SAS AF = 0.000429 (18/41971). AF 95% confidence interval is 0.000277. There are 0 homozygotes in GnomAdExome4. There are 51 alleles in the male GnomAdExome4 subpopulation. Median coverage is 14. This position passed quality control check.
• BS2: High AC in GnomAd4 at 8 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.360+11C>T		intron_variant	Intron 3 of 20	ENST00000357242.10	NP_060222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.360+11C>T		intron_variant	Intron 3 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.0000630 AC: 7 AN: 111035 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000114

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 18 AN: 145084 AF XY: 0.000183

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000306

GnomAD4 exome AF: 0.000170 AC: 157 AN: 923505 Hom.: 0 Cov.: 14 AF XY: 0.000209 AC XY: 51 AN XY: 244123

African (AFR) AF: 0.0000467 AC: 1 AN: 21415

American (AMR) AF: 0.0000376 AC: 1 AN: 26630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17156

East Asian (EAS) AF: 0.00 AC: 0 AN: 27596

South Asian (SAS) AF: 0.000429 AC: 18 AN: 41971

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39582

Middle Eastern (MID) AF: 0.000272 AC: 1 AN: 3673

European-Non Finnish (NFE) AF: 0.000172 AC: 121 AN: 705517

Other (OTH) AF: 0.000375 AC: 15 AN: 39965

GnomAD4 genome AF: 0.0000720 AC: 8 AN: 111087 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33449

African (AFR) AF: 0.0000326 AC: 1 AN: 30684

American (AMR) AF: 0.00 AC: 0 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2625

East Asian (EAS) AF: 0.00 AC: 0 AN: 3524

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5985

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52770

Other (OTH) AF: 0.000662 AC: 1 AN: 1511

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.70
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs369240583; hg19: chrX-106064236;