rs587777767

Variant names:

• chr10-119030538-G-A
• rs587777767
• NM_199461.4:c.737G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_199461.4(NANOS1):​c.737G>A​(p.Arg246His) variant causes a missense change. The variant allele was found at a frequency of 0.00000655 in 1,374,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: NANOS1 NM_199461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 3 publications found

Genes affected

NANOS1 (HGNC:23044): (nanos C2HC-type zinc finger 1) This gene encodes a CCHC-type zinc finger protein that is a member of the nanos family. This protein co-localizes with the RNA-binding protein pumilio RNA-binding family member 2 and may be involved in regulating translation as a post-transcriptional repressor. Mutations in this gene are associated with spermatogenic impairment. [provided by RefSeq, Sep 2015]

NANOS1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 12

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOS1	NM_199461.4	c.737G>A	p.Arg246His	missense_variant	Exon 1 of 1	ENST00000425699.3	NP_955631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOS1	ENST00000425699.3	c.737G>A	p.Arg246His	missense_variant	Exon 1 of 1	6	NM_199461.4	ENSP00000393275.1
NANOS1	ENST00000340087.5	c.113G>A	p.Arg38His	missense_variant	Exon 1 of 1	6		ENSP00000345924.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000655 AC: 9 AN: 1374238 Hom.: 0 Cov.: 33 AF XY: 0.00000878 AC XY: 6 AN XY: 683722

African (AFR) AF: 0.00 AC: 0 AN: 28898

American (AMR) AF: 0.00 AC: 0 AN: 36962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24150

East Asian (EAS) AF: 0.00 AC: 0 AN: 32382

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00000745 AC: 8 AN: 1073176

Other (OTH) AF: 0.00 AC: 0 AN: 56646

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		4.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.18
Sift	Benign	0.35	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;.
Vest4		0.23
MutPred		0.61		Loss of phosphorylation at T248 (P = 0.095);.;
MVP		0.70
ClinPred		0.93	D
GERP RS		4.3
PromoterAI		-0.00090	Neutral
Varity_R		0.25
gMVP		0.51
Mutation Taster		=90/10	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: rs587777767; hg19: chr10-120790050;