6-7590357-G-A

Position:

• chr6-7590357-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152551.4(SNRNP48):​c.100G>A​(p.Ala34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000731 in 1,231,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: SNRNP48 NM_152551.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.763

Genes affected

SNRNP48 (HGNC:21368): (small nuclear ribonucleoprotein U11/U12 subunit 48) Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing. Located in cytosol and nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09116113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP48	NM_152551.4	c.100G>A	p.Ala34Thr	missense_variant	1/9	ENST00000342415.6	NP_689764.3
SNRNP48	XM_047418238.1	c.100G>A	p.Ala34Thr	missense_variant	1/5		XP_047274194.1
SNRNP48	XM_011514312.4	c.93+7G>A		splice_region_variant, intron_variant			XP_011512614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRNP48	ENST00000342415.6	c.100G>A	p.Ala34Thr	missense_variant	1/9	1	NM_152551.4	ENSP00000339834.4
SNRNP48	ENST00000634363.1	n.100G>A		non_coding_transcript_exon_variant	1/8	2		ENSP00000489245.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000731 AC: 9 AN: 1231432 Hom.: 0 Cov.: 29 AF XY: 0.00000332 AC XY: 2 AN XY: 601716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000825

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000405

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000833 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.100G>A (p.A34T) alteration is located in exon 1 (coding exon 1) of the SNRNP48 gene. This alteration results from a G to A substitution at nucleotide position 100, causing the alanine (A) at amino acid position 34 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.019
Sift	Benign	0.096	T
Sift4G	Benign	0.17	T
Polyphen		0.052	B
Vest4		0.20
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0215);
MVP		0.34
MPC		0.30
ClinPred		0.15	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749569883; hg19: chr6-7590590;