1-214364544-C-G

Variant names:

• chr1-214364544-C-G
• rs150646672
• NM_005401.5:c.3403G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005401.5(PTPN14):​c.3403G>C​(p.Glu1135Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E1135K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: PTPN14 NM_005401.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81

Genes affected

PTPN14 (HGNC:9647): (protein tyrosine phosphatase non-receptor type 14) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.3403G>C	p.Glu1135Gln	missense_variant	Exon 18 of 19	ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.3403G>C	p.Glu1135Gln	missense_variant	Exon 18 of 19	1	NM_005401.5	ENSP00000355923.4
PTPN14	ENST00000543945	c.*2679G>C		3_prime_UTR_variant	Exon 17 of 18	5		ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74230

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.83		Gain of MoRF binding (P = 0.2367);
MVP		0.63
MPC		1.0
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.64
gMVP		0.61

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: rs150646672; hg19: chr1-214537887;