chr7-92529591-A-T

Variant names:

• chr7-92529591-A-T
• rs769637128
• NM_032120.4:c.227A>T

Variant summary

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

The NM_032120.4(RBM48):​c.227A>T​(p.Asn76Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,042 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N76S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBM48 NM_032120.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.68
• Publications: 0 publications found

Genes affected

RBM48 (HGNC:21785): (RNA binding motif protein 48) Predicted to enable RNA binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM48	NM_032120.4	c.227A>T	p.Asn76Ile	missense_variant	Exon 2 of 5	ENST00000265732.10	NP_115496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM48	ENST00000265732.10	c.227A>T	p.Asn76Ile	missense_variant	Exon 2 of 5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.227A>T	p.Asn76Ile	missense_variant	Exon 2 of 4	1		ENSP00000419242.1
RBM48	ENST00000496410.1	c.53A>T	p.Asn18Ile	missense_variant	Exon 2 of 3	3		ENSP00000418333.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248386 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

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: 6.86e-7 AC: 1 AN: 1458042 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725458

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.0000225 AC: 1 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109268

Other (OTH) AF: 0.00 AC: 0 AN: 60272

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.8	L;L;.
PhyloP100		6.7
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.016	D;D;T
Sift4G	Uncertain	0.034	D;D;T
Polyphen		1.0	D;.;.
Vest4		0.70
MutPred		0.35		Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);.;
MVP		0.85
MPC		0.83
ClinPred		0.79	D
GERP RS		5.4
Varity_R		0.65
gMVP		0.52
Mutation Taster		=68/32	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: rs769637128; hg19: chr7-92158905;