NM_001164442.2:c.190A>C

Variant names:

• chr5-64690813-A-C
• rs1348338743
• NM_001164442.2:c.190A>C
• SHISAL2B p.Ser64Arg

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001164442.2(SHISAL2B):​c.190A>C​(p.Ser64Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHISAL2B NM_001164442.2 missense, splice_region
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.22
• Publications: 0 publications found

Genes affected

SHISAL2B (HGNC:34236): (shisa like 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164442.2. 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
	SHISAL2B	NM_001164442.2	MANE Select	c.190A>C	p.Ser64Arg	missense splice_region	Exon 1 of 3	NP_001157914.1	A6NKW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISAL2B	ENST00000389074.6	TSL:2 MANE Select	c.190A>C	p.Ser64Arg	missense splice_region	Exon 1 of 3	ENSP00000373726.5	A6NKW6
	SHISAL2B	ENST00000506473.5	TSL:2	n.190A>C		splice_region non_coding_transcript_exon	Exon 1 of 4	ENSP00000426145.1	D6RH14
	SHISAL2B	ENST00000509189.5	TSL:2	n.190A>C		splice_region non_coding_transcript_exon	Exon 1 of 4	ENSP00000426194.1	D6RH14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1360086 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 669420

African (AFR) AF: 0.00 AC: 0 AN: 30170

American (AMR) AF: 0.00 AC: 0 AN: 33114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24042

East Asian (EAS) AF: 0.00 AC: 0 AN: 34382

South Asian (SAS) AF: 0.00 AC: 0 AN: 75624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065976

Other (OTH) AF: 0.00 AC: 0 AN: 56656

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.80	T
PhyloP100		8.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
PromoterAI		-0.012	Neutral
Varity_R		0.87
gMVP		0.68
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.77		Position offset: 1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1348338743; hg19: chr5-63986640;