19-3543480-GCCCCCC-GCCCCCCCC

Variant names:

• chr19-3543480-G-GCC
• rs34196068
• NM_001135580.2:c.322+17_322+18dupCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001135580.2(TEKTIP1):​c.322+17_322+18dupCC 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 0.096 (1407 hom., cov: 0)
  • Exomes 𝑓: 0.083 (541 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2	c.322+17_322+18dupCC		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+8insCC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 11774 AN: 122704 Hom.: 1404 Cov.: 0

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00472

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0864

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0977 AC: 7627 AN: 78042 AF XY: 0.0955

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0131

Gnomad FIN exome AF: 0.0344

Gnomad NFE exome AF: 0.0918

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0827 AC: 99211 AN: 1199538 Hom.: 541 Cov.: 0 AF XY: 0.0831 AC XY: 49136 AN XY: 591164

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

African (AFR) AF: 0.155 AC: 4220 AN: 27294

American (AMR) AF: 0.0875 AC: 2835 AN: 32416

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2199 AN: 21630

East Asian (EAS) AF: 0.00826 AC: 278 AN: 33668

South Asian (SAS) AF: 0.112 AC: 7864 AN: 70042

European-Finnish (FIN) AF: 0.0568 AC: 2111 AN: 37170

Middle Eastern (MID) AF: 0.0954 AC: 339 AN: 3552

European-Non Finnish (NFE) AF: 0.0811 AC: 74842 AN: 923012

Other (OTH) AF: 0.0891 AC: 4523 AN: 50754

⚠️ 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 AF: 0.0960 AC: 11776 AN: 122722 Hom.: 1407 Cov.: 0 AF XY: 0.0923 AC XY: 5442 AN XY: 58968

African (AFR) AF: 0.138 AC: 4122 AN: 29778

American (AMR) AF: 0.0820 AC: 1021 AN: 12452

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 443 AN: 3090

East Asian (EAS) AF: 0.00474 AC: 22 AN: 4642

South Asian (SAS) AF: 0.110 AC: 402 AN: 3644

European-Finnish (FIN) AF: 0.0435 AC: 329 AN: 7562

Middle Eastern (MID) AF: 0.0891 AC: 18 AN: 202

European-Non Finnish (NFE) AF: 0.0871 AC: 5135 AN: 58984

Other (OTH) AF: 0.116 AC: 192 AN: 1650

Alfa AF: 0.0327 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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;