8-30069753-C-A

Variant names:

• chr8-30069753-C-A
• rs572172068
• NM_016127.6:c.589G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016127.6(SARAF):​c.589G>T​(p.Gly197Trp) 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. 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. G197R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SARAF NM_016127.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 0 publications found

Genes affected

SARAF (HGNC:28789): (store-operated calcium entry associated regulatory factor) Involved in regulation of store-operated calcium entry. Located in endoplasmic reticulum and endoplasmic reticulum-plasma membrane contact site. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3587247).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016127.6. 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
	SARAF	NM_016127.6	MANE Select	c.589G>T	p.Gly197Trp	missense	Exon 3 of 6	NP_057211.4
	SARAF	NM_001284239.1		c.73G>T	p.Gly25Trp	missense	Exon 2 of 5	NP_001271168.1	Q96BY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARAF	ENST00000256255.11	TSL:1 MANE Select	c.589G>T	p.Gly197Trp	missense	Exon 3 of 6	ENSP00000256255.6	Q96BY9-1
	SARAF	ENST00000545648.2	TSL:1	c.73G>T	p.Gly25Trp	missense	Exon 2 of 5	ENSP00000441351.1	Q96BY9-2
	SARAF	ENST00000520303.5	TSL:1	n.*296G>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000428963.1	E5RJV6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.51
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.63		Loss of disorder (P = 0.0126)
MVP		0.55
MPC		0.49
ClinPred		0.91	D
GERP RS		2.7
PromoterAI		0.0020	Neutral
Varity_R		0.25
gMVP		0.45
Mutation Taster		=88/12	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: rs572172068; hg19: chr8-29927269; COSMIC: COSV99822747; COSMIC: COSV99822747;