chr19-13895382-C-G

Variant names:

• chr19-13895382-C-G
• rs145816906
• NM_001345843.2:c.196G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001345843.2(BRME1):​c.196G>C​(p.Ala66Pro) 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. 14/21 in silico tools predict a benign 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. A66T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRME1 NM_001345843.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14260331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRME1	NM_001345843.2	c.196G>C	p.Ala66Pro	missense_variant	Exon 3 of 9	ENST00000586783.6	NP_001332772.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRME1	ENST00000586783.6	c.196G>C	p.Ala66Pro	missense_variant	Exon 3 of 9	5	NM_001345843.2	ENSP00000465822.1
BRME1	ENST00000346736.6	c.196G>C	p.Ala66Pro	missense_variant	Exon 3 of 8	2		ENSP00000254336.1
BRME1	ENST00000591586.5	c.196G>C	p.Ala66Pro	missense_variant	Exon 3 of 8	5		ENSP00000466723.1
BRME1	ENST00000585755.1	c.32-2159G>C		intron_variant	Intron 2 of 2	3		ENSP00000466119.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000418 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.7
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.
PhyloP100		-0.27
PROVEAN	Uncertain	-2.6	.;D;.
REVEL	Benign	0.081
Sift	Benign	0.037	.;D;.
Sift4G	Benign	0.065	T;T;T
Polyphen		0.98	.;D;.
Vest4		0.14
MutPred		0.099		Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);
MVP		0.34
MPC		0.19
ClinPred		0.46	T
GERP RS		1.9
Varity_R		0.43
gMVP		0.016
Mutation Taster		=96/4	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: rs145816906; hg19: chr19-14006195;