chr19-3543982-C-T

Variant names:

• chr19-3543982-C-T
• rs190228213
• NM_001135580.2:c.602C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001135580.2(TEKTIP1):​c.602C>T​(p.Pro201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00966 in 1,547,682 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (4 hom., cov: 32)
  • Exomes 𝑓: 0.010 (88 hom.)
• Consequence: TEKTIP1 NM_001135580.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80
• Publications: 5 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]

MFSD12-AS1 (HGNC:56727): (MFSD12 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038712323).
• BP6: Variant 19-3543982-C-T is Benign according to our data. Variant chr19-3543982-C-T is described in ClinVar as Benign. ClinVar VariationId is 2648991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135580.2. 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.602C>T	p.Pro201Leu	missense	Exon 4 of 4	NP_001129052.1	A6NCJ1
	MFSD12	NM_174983.5	MANE Select	c.*728G>A		downstream_gene	N/A	NP_778148.2	Q6NUT3-1
	MFSD12	NM_001287529.2		c.*728G>A		downstream_gene	N/A	NP_001274458.1	Q6NUT3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTIP1	ENST00000329493.6	TSL:2 MANE Select	c.602C>T	p.Pro201Leu	missense	Exon 4 of 4	ENSP00000327950.4	A6NCJ1
	TEKTIP1	ENST00000681976.1		c.443C>T	p.Pro148Leu	missense	Exon 4 of 4	ENSP00000507755.1	A0A804HK34
	MFSD12	ENST00000398558.8	TSL:2	c.328+827G>A		intron	N/A	ENSP00000381566.4	A0A0A0MS91

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 920 AN: 152126 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00582 AC: 892 AN: 153206 AF XY: 0.00589

Gnomad AFR exome AF: 0.00174

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.000488

Gnomad EAS exome AF: 0.000186

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.00645

GnomAD4 exome AF: 0.0101 AC: 14025 AN: 1395438 Hom.: 88 Cov.: 34 AF XY: 0.00995 AC XY: 6842 AN XY: 687892

African (AFR) AF: 0.00171 AC: 54 AN: 31508

American (AMR) AF: 0.00419 AC: 148 AN: 35318

Ashkenazi Jewish (ASJ) AF: 0.000361 AC: 9 AN: 24908

East Asian (EAS) AF: 0.0000841 AC: 3 AN: 35682

South Asian (SAS) AF: 0.00280 AC: 221 AN: 78884

European-Finnish (FIN) AF: 0.00224 AC: 110 AN: 49152

Middle Eastern (MID) AF: 0.00194 AC: 11 AN: 5658

European-Non Finnish (NFE) AF: 0.0121 AC: 13033 AN: 1076484

Other (OTH) AF: 0.00754 AC: 436 AN: 57844

GnomAD4 genome AF: 0.00604 AC: 920 AN: 152244 Hom.: 4 Cov.: 32 AF XY: 0.00541 AC XY: 403 AN XY: 74450

African (AFR) AF: 0.00195 AC: 81 AN: 41558

American (AMR) AF: 0.00634 AC: 97 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 699 AN: 67976

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00846 Hom.: 3

Bravo AF: 0.00671

TwinsUK AF: 0.0119 AC: 44

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.0132 AC: 42

ExAC AF: 0.00354 AC: 128

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.5
DANN	Benign	0.64
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.8
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.018
Sift	Benign	0.37	T
Sift4G	Benign	1.0	T
Polyphen		0.014	B
Vest4		0.15
MVP		0.10
ClinPred		0.0090	T
GERP RS		-4.0
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.6
Varity_R		0.054
gMVP		0.068
Mutation Taster		=99/1	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: rs190228213; hg19: chr19-3543980; COSMIC: COSV99051720; COSMIC: COSV99051720;