rs768789716

Variant names:

• chr19-8445005-G-A
• rs768789716
• NM_005968.5:c.7G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-8445005-G-A
• chr19-8445005-G-T

Variant summary

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

The NM_005968.5(HNRNPM):​c.7G>A​(p.Ala3Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000315 in 1,269,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: HNRNPM NM_005968.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• Publications: 0 publications found

Genes affected

HNRNPM (HGNC:5046): (heterogeneous nuclear ribonucleoprotein M) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNAs. This protein also constitutes a monomer of the N-acetylglucosamine-specific receptor which is postulated to trigger selective recycling of immature GlcNAc-bearing thyroglobulin molecules. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ENSG00000279827 (HGNC:):

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=0.22484869).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005968.5. 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
	HNRNPM	NM_005968.5	MANE Select	c.7G>A	p.Ala3Thr	missense	Exon 1 of 16	NP_005959.2
	HNRNPM	NM_031203.4		c.7G>A	p.Ala3Thr	missense	Exon 1 of 17	NP_112480.2	P52272-2
	HNRNPM	NM_001297418.2		c.-301G>A		5_prime_UTR	Exon 1 of 14	NP_001284347.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPM	ENST00000325495.9	TSL:1 MANE Select	c.7G>A	p.Ala3Thr	missense	Exon 1 of 16	ENSP00000325376.2	P52272-1
	HNRNPM	ENST00000348943.7	TSL:1	c.7G>A	p.Ala3Thr	missense	Exon 1 of 17	ENSP00000325732.2	P52272-2
	HNRNPM	ENST00000940928.1		c.7G>A	p.Ala3Thr	missense	Exon 1 of 15	ENSP00000610987.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000145 AC: 1 AN: 68760 AF XY: 0.0000276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000247

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000315 AC: 4 AN: 1269076 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 619792

African (AFR) AF: 0.00 AC: 0 AN: 25212

American (AMR) AF: 0.00 AC: 0 AN: 13216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18256

East Asian (EAS) AF: 0.00 AC: 0 AN: 29526

South Asian (SAS) AF: 0.00 AC: 0 AN: 58006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4826

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1021606

Other (OTH) AF: 0.0000386 AC: 2 AN: 51762

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000856 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.080
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.10	T
Polyphen		0.88	P
Vest4		0.49
MutPred		0.21		Gain of loop (P = 0.0166)
MVP		0.40
MPC		0.54
ClinPred		0.69	D
GERP RS		5.2
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.47
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768789716; hg19: chr19-8509889;