8-19334705-T-C

Variant names:

• chr8-19334705-T-C
• rs2052416457
• NM_022071.4:c.361T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022071.4(SH2D4A):​c.361T>C​(p.Phe121Leu) 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. 15/22 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. F121V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH2D4A NM_022071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 0 publications found

Genes affected

SH2D4A (HGNC:26102): (SH2 domain containing 4A) Enables phosphatase binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02711761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022071.4. 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
	SH2D4A	NM_022071.4	MANE Select	c.361T>C	p.Phe121Leu	missense	Exon 4 of 10	NP_071354.2
	SH2D4A	NM_001174159.2		c.361T>C	p.Phe121Leu	missense	Exon 4 of 10	NP_001167630.1	Q9H788-1
	SH2D4A	NM_001363110.2		c.361T>C	p.Phe121Leu	missense	Exon 4 of 9	NP_001350039.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4A	ENST00000265807.8	TSL:2 MANE Select	c.361T>C	p.Phe121Leu	missense	Exon 4 of 10	ENSP00000265807.3	Q9H788-1
	SH2D4A	ENST00000519207.5	TSL:1	c.361T>C	p.Phe121Leu	missense	Exon 4 of 10	ENSP00000428684.1	Q9H788-1
	SH2D4A	ENST00000962928.1		c.361T>C	p.Phe121Leu	missense	Exon 4 of 10	ENSP00000632987.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.81
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.68	N
PhyloP100		-0.22
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.015
Sift	Benign	0.61	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.23		Gain of phosphorylation at S124 (P = 0.144)
MVP		0.22
MPC		0.0052
ClinPred		0.018	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.047
Mutation Taster		=93/7	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: rs2052416457; hg19: chr8-19192216;