19-3543910-C-T

Variant names:

• chr19-3543910-C-T
• rs202172544
• NM_001135580.2:c.530C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001135580.2(TEKTIP1):​c.530C>T​(p.Pro177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,551,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: TEKTIP1 NM_001135580.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.329
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06436053).

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.530C>T	p.Pro177Leu	missense	Exon 4 of 4	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.530C>T	p.Pro177Leu	missense	Exon 4 of 4	ENSP00000327950.4	A6NCJ1
	TEKTIP1	ENST00000681976.1		c.371C>T	p.Pro124Leu	missense	Exon 4 of 4	ENSP00000507755.1	A0A804HK34
	MFSD12	ENST00000398558.8	TSL:2	c.328+899G>A		intron	N/A	ENSP00000381566.4	A0A0A0MS91

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000270 AC: 42 AN: 155440 AF XY: 0.000279

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000734

Gnomad FIN exome AF: 0.0000599

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000218 AC: 305 AN: 1398878 Hom.: 1 Cov.: 34 AF XY: 0.000241 AC XY: 166 AN XY: 689972

African (AFR) AF: 0.000190 AC: 6 AN: 31596

American (AMR) AF: 0.000533 AC: 19 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.0000795 AC: 2 AN: 25154

East Asian (EAS) AF: 0.00207 AC: 74 AN: 35732

South Asian (SAS) AF: 0.000215 AC: 17 AN: 79218

European-Finnish (FIN) AF: 0.0000408 AC: 2 AN: 48968

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.000154 AC: 166 AN: 1078850

Other (OTH) AF: 0.000310 AC: 18 AN: 57992

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74438

African (AFR) AF: 0.0000722 AC: 3 AN: 41548

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000157 Hom.: 0

Bravo AF: 0.000196

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.000102 AC: 3

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.33
PROVEAN	Pathogenic	-8.8	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.47
MVP		0.40
ClinPred		0.19	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.61
gMVP		0.14
Mutation Taster		=98/2	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: rs202172544; hg19: chr19-3543908;