chr19-3543982-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

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>A	p.Pro201Gln	missense	Exon 4 of 4	NP_001129052.1	A6NCJ1
	MFSD12	NM_174983.5	MANE Select	c.*728G>T		downstream_gene	N/A	NP_778148.2	Q6NUT3-1
	MFSD12	NM_001287529.2		c.*728G>T		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>A	p.Pro201Gln	missense	Exon 4 of 4	ENSP00000327950.4	A6NCJ1
	TEKTIP1	ENST00000681976.1		c.443C>A	p.Pro148Gln	missense	Exon 4 of 4	ENSP00000507755.1	A0A804HK34
	MFSD12	ENST00000398558.8	TSL:2	c.328+827G>T		intron	N/A	ENSP00000381566.4	A0A0A0MS91

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

African (AFR) AF: 0.00 AC: 0 AN: 31510

American (AMR) AF: 0.00 AC: 0 AN: 35322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24908

East Asian (EAS) AF: 0.00 AC: 0 AN: 35682

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076492

Other (OTH) AF: 0.00 AC: 0 AN: 57844

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.8
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
Mutation Taster		=96/4	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;