rs190228213

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-3543982-C-A
• chr19-3543982-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135580.2(TEKTIP1):​c.602C>A​(p.Pro201Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P201L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TEKTIP1 NM_001135580.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

ENSG00000267436 (HGNC:56727): (MFSD12 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15814397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2	c.602C>A	p.Pro201Gln	missense_variant	Exon 4 of 4	ENST00000329493.6	NP_001129052.1
MFSD12	NM_174983.5	c.*728G>T		downstream_gene_variant		ENST00000355415.7	NP_778148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKTIP1	ENST00000329493.6	c.602C>A	p.Pro201Gln	missense_variant	Exon 4 of 4	2	NM_001135580.2	ENSP00000327950.4
MFSD12	ENST00000355415.7	c.*728G>T		downstream_gene_variant		1	NM_174983.5	ENSP00000347583.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395454 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 687902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.2
DANN	Benign	0.77
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.068
Sift	Uncertain	0.023	D
Sift4G	Benign	0.089	T
Polyphen		0.88	P
Vest4		0.25
MutPred		0.11		Loss of glycosylation at P201 (P = 0.0122);
MVP		0.072
ClinPred		0.82	D
GERP RS		-4.0
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.6
Varity_R		0.11
gMVP		0.092

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

Publications

LitVar

Other links and lift over

dbSNP: rs190228213; hg19: chr19-3543980;