rs775589300

Variant names:

• chr19-13890353-T-C
• rs775589300
• NM_001345843.2:c.503A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001345843.2(BRME1):​c.503A>G​(p.Asp168Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,572,960 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (2 hom.)
• Consequence: BRME1 NM_001345843.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550
• Publications: 0 publications found

Genes affected

BRME1 (HGNC:28153): (break repair meiotic recombinase recruitment factor 1) Predicted to be involved in meiosis I and spermatogenesis. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1690678).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRME1	NM_001345843.2	c.503A>G	p.Asp168Gly	missense_variant	Exon 6 of 9	ENST00000586783.6	NP_001332772.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRME1	ENST00000586783.6	c.503A>G	p.Asp168Gly	missense_variant	Exon 6 of 9	5	NM_001345843.2	ENSP00000465822.1
BRME1	ENST00000346736.6	c.503A>G	p.Asp168Gly	missense_variant	Exon 6 of 8	2		ENSP00000254336.1
BRME1	ENST00000591586.5	c.393+2433A>G		intron_variant	Intron 5 of 7	5		ENSP00000466723.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.00000476 AC: 1 AN: 209892 AF XY: 0.00

Gnomad AFR exome AF: 0.0000642

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000289 AC: 41 AN: 1420800 Hom.: 2 Cov.: 32 AF XY: 0.0000327 AC XY: 23 AN XY: 703772

African (AFR) AF: 0.000744 AC: 24 AN: 32238

American (AMR) AF: 0.00 AC: 0 AN: 39038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23294

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 79476

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

Middle Eastern (MID) AF: 0.000717 AC: 4 AN: 5576

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094068

Other (OTH) AF: 0.000171 AC: 10 AN: 58648

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000825 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.503A>G (p.D168G) alteration is located in exon 6 (coding exon 5) of the C19orf57 gene. This alteration results from a A to G substitution at nucleotide position 503, causing the aspartic acid (D) at amino acid position 168 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		0.055
PROVEAN	Pathogenic	-5.6	.;D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.97	D;D
Vest4		0.10
MutPred		0.10		Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);
MVP		0.41
MPC		0.50
ClinPred		0.46	T
GERP RS		2.1
Varity_R		0.36
gMVP		0.083
Mutation Taster		=100/0	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: rs775589300; hg19: chr19-14001166;