19-3543910-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135580.2(TEKTIP1):​c.530C>A​(p.Pro177Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P177L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TEKTIP1 NM_001135580.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Pro177Gln	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>A	p.Pro177Gln	missense	Exon 4 of 4	ENSP00000327950.4	A6NCJ1
	TEKTIP1	ENST00000681976.1		c.371C>A	p.Pro124Gln	missense	Exon 4 of 4	ENSP00000507755.1	A0A804HK34
	MFSD12	ENST00000398558.8	TSL:2	c.328+899G>T		intron	N/A	ENSP00000381566.4	A0A0A0MS91

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398878 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 689972

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078850

Other (OTH) AF: 0.0000172 AC: 1 AN: 57992

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.33
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.23		Loss of catalytic residue at P177 (P = 0.0088)
MVP		0.21
ClinPred		0.99	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.69
gMVP		0.18
Mutation Taster		=97/3	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;