6-39114941-C-T

Variant names:

• chr6-39114941-C-T
• rs528925283
• NM_018322.3:c.149G>A

Variant summary

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

The NM_018322.3(SAYSD1):​c.149G>A​(p.Arg50Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAYSD1 NM_018322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

SAYSD1 (HGNC:21025): (SAYSVFN motif domain containing 1) Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10675347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018322.3. 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
	SAYSD1	NM_018322.3	MANE Select	c.149G>A	p.Arg50Gln	missense	Exon 1 of 2	NP_060792.1	Q9NPB0-1
	SAYSD1	NM_001304793.2		c.-4460G>A		5_prime_UTR	Exon 1 of 3	NP_001291722.1	Q9NPB0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAYSD1	ENST00000229903.5	TSL:1 MANE Select	c.149G>A	p.Arg50Gln	missense	Exon 1 of 2	ENSP00000229903.4	Q9NPB0-1
	SAYSD1	ENST00000373249.6	TSL:1	n.149G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000362346.2	A0A9H3ZQQ3
	SAYSD1	ENST00000481599.2	TSL:2	n.149G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000515420.1	A0A994J3Z7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.082
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.047
Sift	Benign	0.095	T
Sift4G	Benign	0.13	T
Polyphen		0.054	B
Vest4		0.35
MutPred		0.54		Gain of ubiquitination at K49 (P = 0.0872)
MVP		0.014
MPC		0.13
ClinPred		0.17	T
GERP RS		0.91
PromoterAI		-0.0018	Neutral
Varity_R		0.046
gMVP		0.18
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs528925283; hg19: chr6-39082717;