NM_031272.5:c.3659A>G

Variant names:

• chr17-58571979-T-C
• rs2044541958
• NM_031272.5:c.3659A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031272.5(TEX14):​c.3659A>G​(p.Lys1220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0810
• Publications: 0 publications found

Genes affected

TEX14 (HGNC:11737): (testis expressed 14, intercellular bridge forming factor) The protein encoded by this gene is necessary for intercellular bridges in germ cells, which are required for spermatogenesis. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04550454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031272.5. 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
	TEX14	NM_031272.5	MANE Select	c.3659A>G	p.Lys1220Arg	missense	Exon 24 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.3797A>G	p.Lys1266Arg	missense	Exon 25 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.3779A>G	p.Lys1260Arg	missense	Exon 25 of 33	NP_938207.2	Q8IWB6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX14	ENST00000349033.10	TSL:5 MANE Select	c.3659A>G	p.Lys1220Arg	missense	Exon 24 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.3797A>G	p.Lys1266Arg	missense	Exon 25 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.3779A>G	p.Lys1260Arg	missense	Exon 25 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.071
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.6
DANN	Benign	0.93
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.081
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.024
Sift	Benign	0.24	T
Sift4G	Benign	0.49	T
Polyphen		0.0050	B
Vest4		0.097
MutPred		0.17		Loss of ubiquitination at K1266 (P = 0.0056)
MVP		0.34
MPC		0.045
ClinPred		0.060	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.13

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: rs2044541958; hg19: chr17-56649340;