1-110379330-C-G

Variant names:

• chr1-110379330-C-G
• rs35157487
• NM_004696.3:c.553G>C

Variant summary

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

The NM_004696.3(SLC16A4):​c.553G>C​(p.Ala185Pro) 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. 14/22 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. A185T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A4 NM_004696.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 8 publications found

Genes affected

SLC16A4 (HGNC:10925): (solute carrier family 16 member 4) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR5-AS1 (HGNC:40823): (LAMTOR5 and SLC16A4 antisense RNA 1)

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=0.22361436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004696.3. 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
	SLC16A4	NM_004696.3	MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 6 of 9	NP_004687.1	O15374-1
	SLC16A4	NM_001201546.2		c.409G>C	p.Ala137Pro	missense	Exon 5 of 8	NP_001188475.1	O15374-5
	SLC16A4	NM_001201547.2		c.367G>C	p.Ala123Pro	missense	Exon 5 of 8	NP_001188476.1	O15374-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A4	ENST00000369779.9	TSL:1 MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 6 of 9	ENSP00000358794.4	O15374-1
	SLC16A4	ENST00000472422.6	TSL:1	c.409G>C	p.Ala137Pro	missense	Exon 5 of 8	ENSP00000432495.1	O15374-5
	SLC16A4	ENST00000369781.8	TSL:1	c.526+1652G>C		intron	N/A	ENSP00000358796.4	O15374-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.093
Sift	Uncertain	0.021	D
Sift4G	Benign	0.25	T
Polyphen		0.63	P
Vest4		0.28
MutPred		0.37		Loss of catalytic residue at A185 (P = 0.0639)
MVP		0.60
MPC		0.28
ClinPred		0.47	T
GERP RS		-1.7
PromoterAI		0.0072	Neutral
Varity_R		0.55
gMVP		0.81
Mutation Taster		=93/7	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: rs35157487; hg19: chr1-110921952;