19-3543480-GCCCCCC-GCCCCCCC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000329493.6(TEKTIP1):​c.322+7_322+8insC 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (1049 hom., cov: 0)
  • Exomes 𝑓: 0.13 (632 hom.)
• Consequence: TEKTIP1 ENST00000329493.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 19-3543480-G-GC is Benign according to our data. Variant chr19-3543480-G-GC is described in ClinVar as Benign. ClinVar VariationId is 403083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 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+18dupC		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+7_322+8insC		splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
	MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insG		intron	N/A	ENSP00000381566.4	A0A0A0MS91
	MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insG		intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 11542 AN: 122904 Hom.: 1049 Cov.: 0

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0905

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0885

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0875

GnomAD2 exomes AF: 0.164 AC: 12825 AN: 78042 AF XY: 0.165

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.157

Gnomad FIN exome AF: 0.0952

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.131 AC: 154320 AN: 1180436 Hom.: 632 Cov.: 0 AF XY: 0.132 AC XY: 76632 AN XY: 582056

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

African (AFR) AF: 0.168 AC: 4598 AN: 27392

American (AMR) AF: 0.115 AC: 3653 AN: 31830

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3033 AN: 21598

East Asian (EAS) AF: 0.0642 AC: 2131 AN: 33212

South Asian (SAS) AF: 0.187 AC: 12982 AN: 69396

European-Finnish (FIN) AF: 0.0907 AC: 3366 AN: 37120

Middle Eastern (MID) AF: 0.140 AC: 492 AN: 3524

European-Non Finnish (NFE) AF: 0.130 AC: 117389 AN: 906272

Other (OTH) AF: 0.133 AC: 6676 AN: 50092

⚠️ 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: 0.0939 AC: 11545 AN: 122922 Hom.: 1049 Cov.: 0 AF XY: 0.0930 AC XY: 5493 AN XY: 59056

African (AFR) AF: 0.114 AC: 3394 AN: 29866

American (AMR) AF: 0.103 AC: 1290 AN: 12536

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 368 AN: 3088

East Asian (EAS) AF: 0.0539 AC: 250 AN: 4638

South Asian (SAS) AF: 0.155 AC: 563 AN: 3640

European-Finnish (FIN) AF: 0.0626 AC: 474 AN: 7574

Middle Eastern (MID) AF: 0.0922 AC: 19 AN: 206

European-Non Finnish (NFE) AF: 0.0844 AC: 4977 AN: 59002

Other (OTH) AF: 0.0877 AC: 145 AN: 1654

Alfa AF: 0.0667 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

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

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

Other links and lift over

dbSNP: rs34196068;

hg19: chr19-3543478;