19-3543480-GCCCCCC-GCCCCC

Variant names:

• chr19-3543480-GC-G
• rs34196068
• NM_001135580.2:c.322+18delC

Variant summary

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

The ENST00000329493.6(TEKTIP1):​c.322+8delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (247 hom., cov: 0)
  • Exomes 𝑓: 0.17 (274 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEKTIP1 ENST00000329493.6 splice_region, 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 = 0.097 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000329493.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTIP1	NM_001135580.2	MANE Select	c.322+18delC		intron	N/A	NP_001129052.1	A6NCJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTIP1	ENST00000329493.6	TSL:2 MANE Select	c.322+8delC		splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
	MFSD12	ENST00000398558.8	TSL:2	c.329-504delG		intron	N/A	ENSP00000381566.4	A0A0A0MS91
	MFSD12	ENST00000615073.4	TSL:3	c.490+1328delG		intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 4160 AN: 122714 Hom.: 245 Cov.: 0

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.00418

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.0178

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.00805

Gnomad MID AF: 0.0310

Gnomad NFE AF: 0.00818

Gnomad OTH AF: 0.0298

GnomAD2 exomes AF: 0.229 AC: 17884 AN: 78042 AF XY: 0.233

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.308

Gnomad FIN exome AF: 0.270

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.210

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.168 AC: 171103 AN: 1020834 Hom.: 274 Cov.: 0 AF XY: 0.170 AC XY: 85562 AN XY: 503588

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

African (AFR) AF: 0.162 AC: 4220 AN: 26034

American (AMR) AF: 0.198 AC: 5185 AN: 26246

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 3458 AN: 19046

East Asian (EAS) AF: 0.371 AC: 9797 AN: 26404

South Asian (SAS) AF: 0.142 AC: 8593 AN: 60598

European-Finnish (FIN) AF: 0.225 AC: 7018 AN: 31168

Middle Eastern (MID) AF: 0.186 AC: 582 AN: 3122

European-Non Finnish (NFE) AF: 0.159 AC: 124383 AN: 784408

Other (OTH) AF: 0.180 AC: 7867 AN: 43808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0340 AC: 4167 AN: 122728 Hom.: 247 Cov.: 0 AF XY: 0.0349 AC XY: 2055 AN XY: 58916

African (AFR) AF: 0.100 AC: 2991 AN: 29916

American (AMR) AF: 0.0192 AC: 241 AN: 12532

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 55 AN: 3088

East Asian (EAS) AF: 0.0170 AC: 79 AN: 4638

South Asian (SAS) AF: 0.0546 AC: 199 AN: 3646

European-Finnish (FIN) AF: 0.00805 AC: 60 AN: 7450

Middle Eastern (MID) AF: 0.0340 AC: 7 AN: 206

European-Non Finnish (NFE) AF: 0.00820 AC: 483 AN: 58880

Other (OTH) AF: 0.0296 AC: 49 AN: 1654

Alfa AF: 0.104 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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: rs34196068; hg19: chr19-3543478; COSMIC: COSV61534777; COSMIC: COSV61534777;