NM_001135580.2:c.322+12_322+18dupCCCCCCC

Variant names:

• chr19-3543480-G-GCCCCCCC
• rs34196068
• NM_001135580.2:c.322+12_322+18dupCCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001135580.2(TEKTIP1):​c.322+12_322+18dupCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEKTIP1 NM_001135580.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 3 publications found

Genes affected

TEKTIP1 (HGNC:34496): (tektin bundle interacting protein 1)

MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2	c.322+12_322+18dupCCCCCCC		intron_variant	Intron 2 of 3	ENST00000329493.6	NP_001129052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKTIP1	ENST00000329493.6	c.322+7_322+8insCCCCCCC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4

Frequencies

GnomAD3 genomes AF: 0.000195 AC: 24 AN: 123130 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000797

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: 0.000135

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000181 AC: 22 AN: 1215588 Hom.: 0 Cov.: 0 AF XY: 0.0000200 AC XY: 12 AN XY: 599432

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000249 AC: 7 AN: 28150

American (AMR) AF: 0.0000303 AC: 1 AN: 33012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22134

East Asian (EAS) AF: 0.00 AC: 0 AN: 33838

South Asian (SAS) AF: 0.0000280 AC: 2 AN: 71462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3624

European-Non Finnish (NFE) AF: 0.0000107 AC: 10 AN: 933776

Other (OTH) AF: 0.0000387 AC: 2 AN: 51658

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000195 AC: 24 AN: 123146 Hom.: 0 Cov.: 0 AF XY: 0.000186 AC XY: 11 AN XY: 59168

African (AFR) AF: 0.000501 AC: 15 AN: 29928

American (AMR) AF: 0.0000796 AC: 1 AN: 12568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3092

East Asian (EAS) AF: 0.00 AC: 0 AN: 4642

South Asian (SAS) AF: 0.00 AC: 0 AN: 3650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.000135 AC: 8 AN: 59082

Other (OTH) AF: 0.00 AC: 0 AN: 1660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs34196068; hg19: chr19-3543478;