chr3-122795304-C-T

Variant names:

• chr3-122795304-C-T
• NM_032839.3:c.112C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_032839.3(SLC49A4):​c.112C>T​(p.Pro38Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

SLC49A4 (HGNC:16628): (solute carrier family 49 member 4) This gene encodes a membrane-bound protein from the major facilitator superfamily of transporters. Disruption of this gene by translocation has been associated with haplo-insufficiency and renal cell carcinomas. Alternatively spliced transcript variants have been described, but their biological validity has not yet been determined. [provided by RefSeq, Jul 2008]

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=0.1991247).
• BP6: Variant 3-122795304-C-T is Benign according to our data. Variant chr3-122795304-C-T is described in ClinVar as Benign. ClinVar VariationId is 2445277.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032839.3. 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
	SLC49A4	NM_032839.3	MANE Select	c.112C>T	p.Pro38Ser	missense	Exon 1 of 9	NP_116228.1	Q96SL1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC49A4	ENST00000261038.6	TSL:1 MANE Select	c.112C>T	p.Pro38Ser	missense	Exon 1 of 9	ENSP00000261038.5	Q96SL1-1
	SLC49A4	ENST00000477647.1	TSL:1	n.112C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000418554.1	Q05BS2
	SLC49A4	ENST00000864462.1		c.112C>T	p.Pro38Ser	missense	Exon 1 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1306464 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 643688

African (AFR) AF: 0.00 AC: 0 AN: 25378

American (AMR) AF: 0.00 AC: 0 AN: 17292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21228

East Asian (EAS) AF: 0.00 AC: 0 AN: 29644

South Asian (SAS) AF: 0.00 AC: 0 AN: 68822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050058

Other (OTH) AF: 0.00 AC: 0 AN: 54082

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ovarian cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.89
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.65	T
PhyloP100		3.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Benign	0.68	T
Sift4G	Benign	0.58	T
Vest4		0.17
MutPred		0.33		Gain of phosphorylation at P38 (P = 0.0609)
MVP		0.50
MPC		1.5
ClinPred		0.18	T
GERP RS		2.7
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.47
Mutation Taster		=82/18	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

hg19: chr3-122514151;